Mitochondrial quality control and neurodegenerative diseases

      Our laboratory focuses on understanding the roles of mitochondrial quality control and metabolism in neurodegenerative diseases. We use unbiased proteomics and genomics, cellular and molecular biology, patient iPS cells-derived cell culture and diseased animals to investigate the fundamental mechanisms by which mitochondrial impairment contributes to cellular metabolism disturbance and neurodegeneration. We also utilize rationally designed peptide inhibitors of protein-protein interactions and the high throughput screening approach to developing “mitochondrial medicine” as therapeutic strategies for treating neurodegenerative diseases.

Mitochondria are essential organelles that support cellular function by regulating energy metabolism, generating ATP, and maintaining calcium homeostasis. When mitochondria become dysfunctional, they produce excessive reactive oxygen species and exhibit impaired metabolic activity, which disrupts key biological processes, including cellular bioenergetics, immune responses, genomic stability, and programmed cell death.

To mitigate these detrimental effects, mitochondria employ several quality control mechanisms that preserve their multifaceted functions and alleviate mitochondrial stress. These quality control pathways include mitochondrial dynamics (fusion and fission), the mitochondrial unfolded protein response, and communication with other subcellular organelles. Together, these processes promote the repair of damaged mitochondrial components, facilitate adaptation to stress, and eliminate irreversibly damaged mitochondria.

Our research focuses on elucidating the roles of mitochondrial dynamics–related proteins in maintaining mitochondrial and cellular function, particularly in the context of neurodegenerative diseases. Using a series of inhibitors targeting aberrant mitochondrial fission, we investigate whether modulating mitochondrial dynamics offers a viable therapeutic strategy. In parallel, we apply unbiased proteomic and genomic approaches to identify key regulators of mitochondrial proteostasis and organelle communication, aiming to uncover how mitochondrial protein and genome homeostasis govern cell survival and contribute to the progression of neurodegeneration.